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Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
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Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
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Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
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Journal Article
Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster
2013
Overview
Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of these PTMs have not been characterized. Here we apply a plug-and-play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from
Streptomyces griseus
and discover three new PTMs. This gene cluster is highly conserved in phylogenetically diverse bacterial strains and contains an unusual hybrid polyketide synthase-nonribosomal peptide synthetase, which resembles iterative polyketide synthases known in fungi. To further characterize this gene cluster, we use the same synthetic biology approach to create a series of gene deletion constructs and elucidate the biosynthetic steps for the formation of the polycyclic system. The strategy we employ bypasses the traditional laborious processes to elicit gene cluster expression and should be generally applicable to many other silent or cryptic gene clusters for discovery and characterization of new natural products.
Polycyclic tetramate macrolactams (PTMs) are natural products with important antifungal, antibiotic and antioxidant properties. Here, the authors apply a synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster from
Streptomyces griseus
and identify three putative PTMs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Humanities and Social Sciences
/ Lactams, Macrocyclic - chemistry
/ Lactams, Macrocyclic - isolation & purification
/ Lactams, Macrocyclic - metabolism
/ Peptide Synthases - genetics
/ Polyketide Synthases - genetics
/ Saccharomyces cerevisiae - genetics
/ Science
/ Streptomyces griseus - genetics
